The proposed study is a Type 1 hybrid effectiveness-implementation trial. Individuals with opioid use disorder in county jails throughout the state of Maryland will be randomly assigned within gender within jail to one of two groups: Arm 1. XR-B (n=120). XR-B in jail followed by 6 monthly injections post-release at a community treatment program. Arm 2. XR-NTX (n=120). One injection of XR-NTX in jail, followed by 6 monthly injections post-release at a community treatment program.

This study is a Type 1 hybrid effectiveness-implementation trial. County jails willing to provide extended-release naltrexone (XR-NTX) and extended-release buprenorphine (XR-B) will participate in a randomized controlled trial throughout the state of Maryland, in which 240 incarcerated men and women will be randomly assigned within gender within jail to one of two arms: Arm 1. XR-B (n=120). XR-B in jail followed by 6 monthly injections post-release at a treatment program. Arm 2. XR-NTX (n=120). XR-NTX in jail, followed by 6 monthly injections post-release at a treatment program. In addition to the RCT the investigators will use a learning collaborative to examine the acceptability and feasibility of medications for opioid use disorder (MOUDs). Aim 1. To determine the effectiveness of XR-B compared to XR-NTX in terms of: Primary. (a) pharmacotherapy adherence (number of monthly injections received). Secondary. (b) illicit opioid urine test results; (c) self-reported illicit opioid use; (d) overdose events (non-fatal and fatal); (e) quality of life (i. physical health; ii. mental health); (f) HIV risk behaviors (i. sexual behavior; ii. needle use or sharing); and (g) criminal activity (i. crime days; ii. re-arrest; iii. re-incarceration). Aim 2. To use a learning collaborative involving all 7 RCT county jurisdictions as well as 3 additional counties that selected not to participate in the randomized trial to understand factors related to: (a) acceptability of providing long-acting agonists and antagonists in jail settings; and (b) feasibility of providing medication continuity of care from jail to community treatment providers. Aim 3. Calculate the cost to the correctional health system of implementing an XR-B or XR-NTX program, and determine the relative value of each strategy, including the costs associated with the subsequent interventions in the community, from a state-policymaker and societal perspective.

Inclusion Criteria:

• Adult male or female inmates at participating jails who are eligible for release within 120 days
• History of opioid use disorder (meeting DSM-5 criteria of moderate or severe opioid use disorder at the time of incarceration; individuals not meeting the opioid-disorder criterion will be eligible if they were treated in an opioid agonist treatment program during the year before incarceration)
• Suitability for XR-B and/or XR-NTX treatment as determined by medical evaluation
• Willingness to enroll in XR-B or XR-NTX treatment in jail
• Planning to live in one of the 7 participating counties and/or surrounding counties

Exclusion Criteria:

• Liver function test levels greater than 4 times normal;
• Active medical illness that may make participation hazardous (e.g., unstable diabetes, heart disease; moderate to severe renal impairment; adequately treated medical conditions are acceptable);
• Conditions or medications that may predispose to QTc prolongation (personal or family history of long QT syndrome, hypokalemia, medications that prolong QTc interval, e.g., macrolide antibiotics, azole antifungal compounds, anti-arrythmics, antipsychotics and antidepressant)
• Untreated psychiatric disorder that may make participation hazardous (e.g., untreated psychosis, bipolar disorder with mania; adequately treated psychiatric disorders and appropriate psychotropic medications will be allowed);
• History of allergic reaction to naltrexone and/or buprenorphine;
• Current chronic pain diagnosis for which opioids are prescribed;
• Pregnancy (for women);
• Breast-feeding (for women);
• Suicidal ideation (within the past 6 months);
• Body Mass Index (BMI) > 40;
• Inability to pass a study enrollment quiz;
• Currently enrolled in jail-based MOUD pharmacotherapy (methadone, buprenorphine, naltrexone)
• Enrolled in a methadone treatment program in the past 30 days.